1. Field of the Invention
This invention relates to a method for treating hypertension by the administration of aminoalkyl phenyl sulfide derivatives. Moreover, it relates to a method for evaluating the effectiveness of these compounds through oxygenation by dopamine-beta-hydroxylase.
2. Description of the Prior Art
Logical approaches to the treatment of hypertension require an understanding of the biochemistry and enzymology of the body as it relates to the problems of high blood pressure. Prior art discloses the presence of compounds containing phenyl sulfides and amino groups biologically active as anti-microbial agents, anti-depressives, appetite suppressants, anti-hypertensives and anti-inflammatory agents.
Wehrmeister U.S. Pat. No. 3,318,953 and U.S. Pat. No. 4,260,634 discloses a method of synthesis of phenylthioalkylamines and amides thereof together with their use as anti-fungal and anti-bacterial agents in metal-working oil or chemical lubricants. No disclosure relating to a pharmacological use is made.
Nair et al. U.S. Pat. No. 3,519,686 discloses 1-(4-chlorophenyl)-mercapto-2-propylamine and salts thereof for use as an anti-depressive or mood elevator. However, these compounds are not disclosed as anti-hypertensive agents for use in lowering blood pressure.
Andrisano, U.S. Pat. No. 3,911,015, discloses the use of alkanol-thio-alkylamines and their salts as therapeutic agents useful in treating peripheral vasodilatory and hypertensive problems. Andrisano discloses compounds containing 2 aromatic rings connected by an alkyl chain containing a thio and a nitro group. This compound is clearly distinguishable from the aminoalkyl phenyl sulfide derivatives of the present invention in that the two aromatic groups are required as well as the presence of an alkyl group connecting the nitrogen to the phenol group.
Lafon, U.S. Pat. No. 4,065,584 discloses anorexigenic agents (appetite supressants) and analgesic or anti-inflammatory properties of sulphur-containing arylamine derivatives. These compounds all include a nitrogen-containing saturated heterocyclic ring. Therefore, the compounds and utilities disclosed by Lafon are different from those of the present invention.
Neustadt, U.S. Pat. No. 4,199,597 discloses polyfluoro substituted phenoxy and phenylthio alkanoic acids having antihypertensive activity. These compounds are structurally different from those of the present invention in that a polyfluoro-containing group is present on the aromatic ring.
The prior art fails to disclose a unifying approach to hypertensive treatment as is found in the present invention. The prior art does not disclose the use of the aminoalkyl phenyl sulfide derivatives of the present invention as antihypertensive agents. In a broader sense the present invention contains the insight of evaluating a compound as a substrate for dopamine-beta-hydroxylase. This use of a purified enzyme system to oxygenate the sulfur group reflects a strategy of analysis which permits evaluation of both the enzymatic parameters and products formed by dopamine-beta-hydroxylase when acting on the compound of interest. This permits the design of therapeutic strategies involving the specific aminoalkyl phenyl sulfides disclosed and enzymes that modify them such as the dopamine-beta-hydroxylase and monoamine oxidase. Therefore, this invention also satisfies a need for a fast and effective method of evaluating the disclosed hypotensive compounds in vitro and allows a more precise method for developing effective treatment of hypertension.